A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)

Herpes Simplex Virus Clinical Trial

Official title:

A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01610765
• Other study ID #: DMID 11-0068
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: May 30, 2012
• Last updated: June 6, 2016
• Start date: January 2016
• Est. completion date: June 2017

Study information

• Verified date: June 2016
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This study is to identify if a Novel Antiviral Drug could be used to treat babies with Herpes Simplex Virus (HSV) with central nervous system (CNS) disease. In this study the investigators will identify the best dose for young children as well as identify additional safety information about the Novel Antiviral Drug.

Description:

In this study, the pharmacokinetics and safety of a Novel Antiviral Drug will be determined in babies with neonatal HSV CNS disease. The study will be conducted at 18 academic medical centers throughout the United States. Young infants presenting with virologic confirmation of neonatal HSV infection and evidence of CNS involvement will be eligible for study enrollment. Study Day 1 is defined as the day when dose 1 of the Novel Antiviral Drug study medication is administered.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 98 Days

Eligibility

Inclusion Criteria:

• Signed Informed Consent by parent or legal guardian of study subject

• Virologically confirmed HSV infection [e.g., positive culture, DNA detection by polymerase chain reaction (PCR), or direct fluorescent antibody stain from any body site or compartment]

• Evidence of CNS involvement of HSV disease [e.g., CSF pleocytosis, positive CSF PCR testing, clinical or electroencephalogram (EEG) seizure activity, neuroimaging abnormality)

• Starting parenteral acyclovir therapy at time of initiation of CMX001 study drug or receiving parenteral acyclovir therapy for = 72 hours before start CMX001 study drug

• = 6 weeks (42 days) of age at time of initial onset of disease symptoms or signs

• Weight at study enrollment = 2,630 grams

• Gestational age = 36 weeks at delivery

• Mother tested negative for HIV during or following pregnancy

Exclusion Criteria:

• Imminent demise

• Disseminated or skin/eye/mouth (SEM) neonatal HSV disease classifications

• Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., history of necrotizing enterocolitis, gastroschisis, malrotation, etc.)

• Birth weight < 2,500 grams

• Birth weight > 4,500 grams

• Grade 3 or 4 vomiting, utilizing the DAIDS Toxicity Tables (Appendix B)

• Grade 3 or 4 diarrhea, utilizing the DAIDS Toxicity Tables (Appendix B)

• Creatinine clearance < 15 mL/min/1.73m2

• Serum albumin < 2.0 g/dL

• Alanine aminotransferase (ALT) = 2.6-times upper limit normal (ULN)

• Aspartate aminotransferase (AST) = 2.6-times upper limit normal (ULN)

• Direct bilirubin > 2 mg/dL

• Known immunodeficiency

• Known congenital infection (e.g., symptomatic congenital cytomegalovirus infection; syphilis; congenital toxoplasmosis)

• Congenital heart disease (e.g., patent ductus arteriosus, Tetralogy of Fallot, hypoplastic left heart syndrome, AV canal, VSD, ASD, transposition of the great arteries, hypoplastic right ventricle, truncus arteriosus, pulmonic stenosis, Ebstein anomaly, coarctation of the aorta, interrupted aortic arch, double outlet right ventricle, dilated cardiomyopathy)

• Infants currently receiving or anticipated to need treatment with digoxin that cannot be withheld for the duration of CMX001 therapy

• Infants currently receiving or anticipated to need treatment with ketaconazole that cannot be withheld for the duration of CMX001 therapy

• Receipt of investigation drugs within 30 days prior to enrollment

• Concurrent enrollment or participation in any other interventional research study

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Herpes Simplex
• Herpes Simplex Virus

Intervention

Drug:
• Novel Antiviral Drug
4 oral doses of a Novel Antiviral Drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.
• Placebo
4 oral doses of placebo matching the a Novel Antiviral Drug assigned dose: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.

Locations

Country	Name	City	State
United States	Emory Children's Center	Atlanta	Georgia
United States	University of Colorado at Denver Health Sciences Center	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Carolinas Medical Center - Charlotte	Charlotte	North Carolina
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	University of Texas-Southwestern	Dallas	Texas
United States	Dartmouth Medical School	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Steven & Alexandra Cohen Children's Medical Center Of New York (CCMC)	Manhasset	New York
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	Louisiana State University Health Science Center -Shreveport	Shreveport	Louisiana
United States	Washington University in St Louis School of Medicine	St. Louis	Missouri
United States	University of South Florida School of Medicine	Tampa	Florida
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.		Baseline through day 21	No
Primary	Determine the plasma pharmacokinetics of the CMX001 and cidofovir following administration of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.		Baseline through day 21	No
Secondary	Explore a plasma drug concentration-response relationship between CMX001 exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy		Baseline through day 21	No
Secondary	Explore a plasma drug concentration-response relationship between cidofovir exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy		Baseline through day 56 (end of study)	Yes